Prospective One-Health investigation into low-abundant extended-spectrum β-lactamase producing Enterobacterales enables detection of potential dissemination events and persistence.

Background: Following a one-health approach, we sought to determine reservoirs of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), other than Escherichia coli or Klebsiella pneumoniae complex species (i.e., low-abundant species), and their associated ESBL genes and plasmid-replicon profiles.

Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients.

Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records.

Extended-spectrum β-lactamase-producing Enterobacterales in diverse foodstuffs: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The involvement of non-human-to-human transmission of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread.

Aim: We aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city.

Spatiotemporal dissemination of ESBL-producing Enterobacterales in municipal sewer systems: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The contribution of community and hospital sources to the transmission of extended-spectrum β-lactamase producing Enterobacterales (ESBL-PE) remains elusive.

Aim: To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel.

Methods: Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites,  = 17) or community and hospital wastewater (mixed sites,  = 4).

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.

Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland.

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C.

Identification of a Cluster of Extended-spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Sequence Type 101 Isolated From Food and Humans.

We report a cluster of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sequence type 101, derived from 1 poultry and 2 clinical samples collected within the setting of a prospective study designed to determine the diversity and migration of ESBL-producing Enterobacterales between humans, foodstuffs, and wastewater.

Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements-identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland.

Introduction: Extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae were first described in relation with hospital-acquired infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as especially ESBL-producing was increasingly described as an important cause of community-acquired infections, supporting the hypothesis that in more recent years ESBL-producing Enterobacteriaceae have probably been imported into hospitals rather than vice versa. Transmission of ESBL-producing Enterobacteriaceae is complicated by ESBL genes being encoded on self-transmissible plasmids, which can be exchanged among the same and different bacterial species.

Cognitive impairment in heart failure: results from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) randomized trial.

Aims: Up to 50% of patients with heart failure (HF) may suffer from severe cognitive impairment (SCI), but longitudinal studies are sparse, and effects of changes in HF severity on cognitive function are unknown. Therefore, we assessed the prevalence of SCI in HF patients, its relationship with HF severity, its effects on morbidity and mortality, and the relationship between changes in HF severity and cognitive function.

Methods And Results: We included 611 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) and assessed cognitive function [Hodkinson Abbreviated Mental Test (AMT)] in relation to severity of HF (NYHA class, NT-proBNP) at baseline and 18 months (n = 382) and effects on hospitalization-free survival and mortality.

Why and how do elderly patients with heart failure die? Insights from the TIME-CHF study.

Aims: Specific causes and modes of death (COD and MOD) of patients with heart failure (HF) are not well described, particularly in those with preserved ejection fraction >45% (HFPEF) and at old age. Thus, using the database of the TIME-CHF study, patients with HFPEF were compared with those with reduced ejection fraction ≤45% (HFREF), and patients ≥75 with those 60-74 years of age to identify MOD and COD, predictors of death, and event rates before death as compared with survivors.

Methods And Results: During the 18-month follow-up, 132/622 patients (21%) died, with similar rates in patients with HFPEF and HFREF and a trend to higher rates in patients aged ≥75 years (24% vs.

End-of-life preferences of elderly patients with chronic heart failure.

Aims: Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for quality-of-life (QoL) and the preferences for resuscitation.

Methods And Results: At baseline and after 12 and 18 months, 622 HF patients aged ≥60 years (77 ± 8 years, 74% NYHA-class ≥III) participating in the Trial of Intensified vs.

Detection of intake of nonsteroidal anti-inflammatory drugs in elderly patients with heart failure. How to ask the patient?

Principles: Heart failure hospitalisations may be related to non-steroidal anti-inflammatory drug (NSAID) use. Since NSAIDs are usually prescribed by general practitioners or taken without prescription, their use may be largely underestimated. Therefore, we assessed the impact of a focussed analgesic medication history as compared to a usual medication history on detection of NSAID intake in elderly heart failure patients and the potential effect of medical advice on discontinuation of this therapy in a non-controlled study design.

BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.

Context: It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy.

Objective: To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy.

Design, Setting, And Patients: Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal.

Influence of acute and chronic mineralocorticoid excess on endothelial function in healthy men.

Aldosterone has rapid nongenomic effects in the human vasculature. However, data are not uniform and little is known about chronic effects of aldosterone. Therefore, we investigated acute and chronic effects of elevated aldosterone levels on endothelial function in the forearm vasculature of healthy men.

Management of elderly patients with congestive heart failure--design of the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF).

Background: Little is known about the management of elderly patients with congestive heart failure (CHF) although they represent the majority of the CHF population. Therefore, the TIME-CHF study was set up (1) to evaluate the medical management of very old patients (> or = 75 years) with CHF compared with younger patients (60-74 years), (2) to compare an intensified with a standard treatment approach, and (3) to differentiate between systolic and diastolic dysfunction (ejection fraction < or = 45% vs > 45%).

Methods: In a prospective single-blinded multicenter trial, 824 symptomatic patients, CHF hospitalization within the last year and elevated NT-BNP, are randomized to an intensified versus a standard medical therapy.

Systemic endothelial dysfunction in adults with cyanotic congenital heart disease.

Background: Secondary erythrocytosis results in increased shear stress in cyanotic congenital heart disease (CCHD), which may modify the balance between vasodilators and vasoconstrictors and affect systemic endothelial function. Because no data are available on systemic vasomotion, systemic endothelial function and nitric oxide (NO) availability were investigated in CCHD patients.

Methods And Results: Responses to arterial endothelium-dependent (acetylcholine [Ach]) and -independent (sodium nitroprusside [SNP]) vasodilation, NO synthase blockade (NG-monomethyl-L-arginine [L-NMMA]), endothelin-1 (ET-1), and ET-1 receptor blockade by BQ-123 in 11 CCHD patients (O2 saturation <90%; mean+/-SD, 79+/-1%; mean+/-SD age, 39+/-2 years) were compared with those in 10 age-matched healthy referents by using forearm venous occlusion plethysmography.

Vascular effects of natriuretic peptides in healthy men.

Background: Most effects of atrial (ANP) and B-type natriuretic peptide (BNP) result from stimulation of the guanylyl-cyclase type A receptor. Chronic elevation causes hyporesponsiveness to ANP, whereas BNP effects tend to be preserved, implying an additional pathway of action. We, therefore, investigated the hemodynamic effects of co-infusion of ANP, BNP, and, as a positive control acting on type B receptor, C-type natriuretic peptide (CNP).

Interaction of sildenafil with cAMP-mediated vasodilation in vivo.

Sildenafil inhibits cGMP breakdown by phosphodiesterase 5. In vitro, increased cGMP levels inhibit cAMP breakdown by phosphodiesterase 3. It is uncertain, however, whether sildenafil increases biological effects of interventions increasing cAMP levels in vivo.